Role of the Endocannabinoid System in Metabolic Control Processes and in the Pathogenesis of Metabolic Syndrome: An Update

Metabolic syndrome is a complex disease state, which appears mostly as a consequence of an unhealthy, sedentary lifestyle. Metabolic complications include insulin resistance (IR), diabetes, dyslipidemia, hypertension, and atherosclerosis, impairing life standards and reducing life expectancy. The endocannabinoid system (ECS) has an important role in signalization processes, not only in the central nervous system, but also in the peripheral tissues. Several physiological functions are affected, and overexpression or downregulation contributes to several diseases. A better understanding of the functions of cannabinoid (CB) receptors may propose potential therapeutic effects by influencing receptor signaling and enzymes involved in downstream pathways. In this review, we summarize recent information regarding the roles of the ECS and the CB1 receptor signaling in the physiology and pathophysiology of energy and metabolic homeostasis, in the development of obesity by enhancing food intake, upregulating energy balance and fat accumulation, increasing lipogenesis and glucose production, and impairing insulin sensitivity and secretion. By analyzing the roles of the ECS in physiological and pathophysiological mechanisms, we introduce some recently identified signaling pathways in the mechanism of the pathogenesis of metabolic syndrome. Our review emphasizes that the presence of such recently identified ECS signaling steps raises new therapeutic potential in the treatment of complex metabolic diseases such as diabetes, insulin resistance, obesity, and hypertension.